Dacarbazine

Dacarbazine is a non-cell cycle specific antineoplastic agent. The exact mechanism of action by which it exerts cytotoxic effects is still unclear. However, three possible mechanisms have been postulated, including inhibition of DNA synthesis by acting as a purine analog, action as an alkylating agent, and interaction with sulfydryl group in the inhibition of bacterial cell growth. It appears to form methylcarbonium ions that attack nucleophilic groups by attaching to the 7-position of guanine on DNA. It also cross-links DNA strands leading to inhibition of DNA, RNA and protein synthesis.

• Metastatic malignant melanoma
• Hodgkin's disease (second-line therapy)
• Soft tissue sarcoma

Dacarbazine is a non-cell cycle specific antineoplastic agent. The exact mechanism of action by which it exerts cytotoxic effects is still unclear. However, three possible mechanisms have been postulated, including inhibition of DNA synthesis by acting as a purine analog, action as an alkylating agent, and interaction with sulfydryl group in the inhibition of bacterial cell growth.

Dacarbazine forms methylcarbonium ions that attack nucleophilic groups by attaching to the 7-position of guanine on DNA and cross-links DNA strands, leading to inhibition of DNA, RNA and protein synthesis, thereby stopping cancer cell growth and multiplication.

Adult - Malignant Melanoma: 2-4.5 mg/kg/day IV for 10 days, repeat at 4-week intervals; OR 250 mg/m²/day IV for 5 days, repeat at 3-week intervals; OR 850 mg/m² IV infusion, repeat at 3-week intervals.

Adult - Hodgkin's Disease: 150 mg/m²/day IV for 5 days, repeat every 4 weeks; OR 375 mg/m² IV on Day 1, repeat every 15 days (in combination with other agents).

Adult - Soft Tissue Sarcoma: 250 mg/m²/day IV for 5 days, repeated every 3 weeks (usually given with doxorubicin).

Child - Hodgkin's Disease: 150 mg/m² IV daily for 5 days, repeat every 4 weeks; OR 375 mg/m² IV on Day 1, repeat every 15 days (as part of ABVD regimen).

This medicine is given as an intravenous injection or infusion. Your doctor or nurse will give you this medicine. Kindly do not self administer.

If you miss a dose of Dacarbazine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Common Side Effects:

• Nausea and vomiting (>90% of patients)
• Injection site pain
• Decreased white blood cell count
• Loss of appetite
• Diarrhea (rare)

Serious Side Effects:

• Bone marrow suppression
• Tissue damage (extravasation)
• Hypersensitivity reactions

• May affect your ability to drive due to CNS side effects.
• Extravasation during intravenous administration may result in tissue damage and severe pain.
• Adequate laboratory study capability must be available during treatment.
• Avoid during pregnancy and lactation.
• Effective contraception by both males and females is important.

• Hypersensitivity
• Bone marrow suppression

Enzyme inducers (barbiturates, rifampicin, phenytoin): Increased metabolism.

Mercaptopurine, azathioprine, allopurinol: May potentiate the effect.

Vaccines: Impairs immune response; infection possible after live vaccines.

Methoxsalen: May enhance effects due to photosensitisation.

CYP1A2 inhibitors (amiodarone, ciprofloxacin, fluvoxamine, ketoconazole, lomefloxacin, ofloxacin, rofecoxib): Increased effect.

CYP1A2 inducers (aminoglutethimide, carbamazepine, phenobarbital, rifampicin): Decreased effect.

Caution is advised when consuming alcohol with Dacarbazine. Please consult your doctor.

Pregnancy Category C. Dacarbazine may be unsafe during pregnancy. Animal studies have shown fetal abnormalities. Your doctor will weigh the benefits and any potential risks. Please consult your doctor.

Dacarbazine is probably unsafe during breastfeeding. It is not known whether this drug is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug.

Dosage for Hodgkin's disease in children is established (as part of ABVD regimen). Limited information available for other pediatric indications.

No specific dosage adjustment is necessary for elderly patients. However, caution should be exercised.

Renal impairment: Use with caution. Dose adjustment may be needed. Please consult your doctor.

Hepatic impairment: Use with caution. Dose adjustment may be needed. Please consult your doctor.

Overdose may lead to severe bone marrow suppression, gastrointestinal toxicity and vomiting. Give supportive treatment and monitor blood cell counts.

Store in a refrigerator at 2°C to 8°C. After reconstitution, may be stored at 4°C for up to 72 hours or at room temperature for up to 8 hours.

Dacarbazine